蛋白质的翻译后修饰(PTM)对于微调细胞对细胞内和细胞外信号的反应至关重要。ADP-核糖基化是一种PTM,它以两种风味发生:用多个ADP-核糖部分(聚(ADP-核糖基)或PARylation)或只有一个单元(MARylation)修饰靶标,它们由PARP家族(也称为ARTD家族)的不同酶添加。PARylation已经得到了相对充分的研究,特别是在DNA损伤反应中。这导致了PARP抑制剂如奥拉帕尼的发展,越来越多地用于癌症化疗方法。尽管大多数PARP酶催化MARylation,MARylation没有PARylation那么好理解。MARylation是一个动态过程:2013年发现了逆转酸性氨基酸(MACROD1,MACROD2和TARG1)细胞内MARylation的酶。从那以后,然而,关于它们的生理功能的信息很少。MACROD1,MACROD2和TARG1具有一个包含催化位点的“宏结构域”,但没有确定其他领域。尽管缺乏有关其细胞作用的信息,有许多研究将它们与癌症联系起来。然而,其中一些出版物相互对立,有些依赖于特征不佳的抗体,或过表达而不是天然蛋白质的异常定位。在这次审查中,我们批判性地评估了关于水解酶在癌症中的作用的现有文献,目前,关于MACROD1、MACROD2或TARG1在肿瘤发生中的作用的证据有限。
Post-translational modifications (PTM) of proteins are crucial for fine-tuning a cell\'s response to both intracellular and extracellular cues. ADP-ribosylation is a PTM, which occurs in two flavours: modification of a target with multiple ADP-ribose moieties (poly(ADP-ribosyl)ation or PARylation) or with only one unit (MARylation), which are added by the different enzymes of the PARP family (also known as the ARTD family). PARylation has been relatively well-studied, particularly in the DNA damage response. This has resulted in the development of PARP inhibitors such as olaparib, which are increasingly employed in cancer chemotherapeutic approaches. Despite the fact that the majority of PARP enzymes catalyse MARylation, MARylation is not as well understood as PARylation. MARylation is a dynamic process: the enzymes reversing intracellular MARylation of acidic amino acids (MACROD1,
MACROD2, and TARG1) were discovered in 2013. Since then, however, little information has been published about their physiological function. MACROD1,
MACROD2, and TARG1 have a \'macrodomain\' harbouring the catalytic site, but no other domains have been identified. Despite the lack of information regarding their cellular roles, there are a number of studies linking them to cancer. However, some of these publications oppose each other, some rely on poorly-characterised antibodies, or on aberrant localisation of overexpressed rather than native protein. In this review, we critically assess the available literature on a role for the hydrolases in cancer and find that, currently, there is limited evidence for a role for MACROD1,
MACROD2, or TARG1 in tumorigenesis.